Gingival Hyperplasia As an Early Manifestation of Acute Myeloid Leukemia. a Retrospective Review

J Clin Exp Dent. 2019;11(12):e1139-42. Gingival hyperplasia and acute myeloid leukemia

Journal section: Community and Preventive Dentistry doi:10.4317/jced.56214 Publication Types: Research https://doi.org/10.4317/jced.56214

Gingival hyperplasia as an early manifestation of acute myeloid leukemia. A retrospective review

Nansi López-Valverde 1, Antonio López-Valverde 1, Rafael Gómez-de Diego 2, Juan M. Ramírez 3, Javier Flores-Fraile 1, Jorge Muriel-Fernández 1

1 Department of Surgery, Instituto de Investigación Biomédica de Salamanca (IBSAL), University of Salamanca, Salamanca, Spain 2 Department of Oral Medicine. Rey Juan Carlos University, Madrid, Spain 3 Department of Morphological Sciences. University of Cordoba, Cordoba, Spain

Correspondence: Avda. Alfonso X El Sabio S/N. 37007 Salamanca, Spain [email protected] López-Valverde N, López-Valverde A, Gómez-de Diego R, Ramírez JM, Flores-Fraile J, Muriel-Fernández J. Gingival hyperplasia as an early manifestation of acute myeloid leukemia. A retrospective review. J Clin Exp Received: 21/08/2019 Accepted: 04/11/2019 Dent. 2019;11(12):e1139-42. http://www.medicinaoral.com/odo/volumenes/v11i12/jcedv11i12p1139.pdf

Article Number: 56214 http://www.medicinaoral.com/odo/indice.htm © Medicina Oral S. L. C.I.F. B 96689336 - eISSN: 1989-5488 eMail: [email protected] Indexed in: Pubmed Pubmed Central® (PMC) Scopus DOI® System

Abstract Background: We study the prevalence of acute myeloid leukemia (AML) among patients with severe gingival enlargement. Material and Methods: We retrospective reviewed the clinical records of patients with severe gingival enlargement, between 2011 and 2018. The Saxer and Mühlemann index were used to measure inflammation and gingival bleeding. The degree of dental mobility was measured by the Nyman and Lindhe technique. Results: A correlation analysis was carried out to test whether there were any associations among the different variables. In the sample of 117 patients the mean gingival bleeding index was ≥3 and the degree of dental mobility ≥2.3. 1.7% of patients, with severe gingival hyperplasia were diagnosed with AML. We found a significant association between gingival bleeding and aging (p<0.001) and a trend (0.54) between bleeding and suffering from AML. Conclusions: Severe gingival enlargement, abundant gingival bleeding, and dental mobility could be early manifestations of a blood dyscrasia.

Key words: Acute myeloblastic leukemia, gingival hyperplasia, bleeding, tooth motility, oral health.

Introduction The new classification scheme for periodontal diseases It essential for clinicians to have a sound knowledge of includes the subsection Hematological Conditions under periodontal diseases, not only so that they are able to the section Gingivitis mediated by systemic or local risk diagnose this type of pathologies, but also so that they factors (1,2). may, in certain cases, learn their real origin when they The current classification associates aggressive perio- appear as the first sign of a specific systemic disease. dontitis (AP) with a low bacterial plaque burden but

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with highly virulent bacteria such as porphyromonas All the patients underwent periodontal exploration ac- gingivalis, actinobacillus actinomycetemcomitans or cording to a specific protocol, SEPA Code 4 (Spanish tannerella forsythia. The difference between the locali- Society of Periodontology and Osseointegration), which zed and the generalized forms only refers to the number consisted of a thorough periodontal study (periodontal of affected teeth (3). chart, plaque index, gum bleeding, dental mobility, or- Leukemia is a hematological malignancy caused by the thopantomography and an intraoral series of X-rays). In proliferation of the tissues that form white blood cells, particular those that showed a bag probing greater than leading to a sharp increase in circulating immature white 6 mm in 1 or more teeth of a sextant were considered as blood cells. patients with severe gingival hyperplasia. Inflammation Acute myeloblastic leukemia (AML) is the most com- and gingival bleeding indices were measured using mon type of acute leukemia in adults. The bone marrow Saxer and Mühlemann’s Papillary Bleeding Index (PBI), is naturally responsible for producing a certain type of which has proved very useful in public health programs cells known as myeloblasts, which mature into granu- (6). Tooth mobility was measured through the individual locytes. In AML, myeloblasts proliferate abnormally, mechanical method, consisting of using two fingers to progressively invading the bone marrow and interfering apply pressure on the crown of the tooth, followed by with the production of normal blood cells. pressure in the buccolingual direction, registering the The incidence estimate is 2-3 cases/100,000 per year, degree of tooth mobility according to the technique re- gradually increasing with age to a peak of 12.6/100000 commended by Nyman and Lindhe (7). in patients aged over 65 years old (4). Patients were later referred to their corresponding pri- In addition to oral ulceration and infection and gingival mary healthcare centers to be finally examined and bleeding, oral and periodontal manifestations of leuke- assessed by the Hematology Service of the Clinical mia consist of infiltration of gingivae by leukemic cells, University Hospital before establishing appropriate pe- resulting in gingival overgrowth, which develops into riodontal treatment. pseudo-pockets where dental biofilm accumulates pro- Pearson correlation using SPSS© 21.0.0.0 with a statis- ducing, in turn, a second inflammatory lesion that contri- tical significance threshold of p<0.05 was used to check butes to gum enlargement, so that, gingival enlargement correlations among tooth mobility, gum bleeding index, is as much the result of leukemic infiltration as of reacti- age and suffering from ALM. ve gingival hyperplasia. Informed consent, formalized at the Dental Clinic, was Identifying gingival overgrowth as an initial oral mani- obtained from all the patients participating in the study festation of leukemic infiltration is extremely important and was approved by the Bioethics Committee of the for establishing an early diagnosis of acute leukemia (5). University of Salamanca in accordance with the Helsin- Therefore, with this study our aim is to review the preva- ki Declaration of 1964. lence of acute myeloid leukemia (AML) among patients with severe gingival enlargement treated in a dental cli- Results nic. The study, based on a large initial sample of 16,364 patients, identified severe gingival hyperplasia in 0.71% Material and Methods (n=117), of whom 1.7% (n=2) were diagnosed with A retrospective review was carried out at the Dental Cli- AML. The exploratory data reflected tooth mobility ave- nic of the University of Salamanca between 2011 and rages of ≥2.4 in women and ≥2.3 in men. The average 2018 (both years included) based on a sample of 16,364 bleeding index was ≥2.9 in women and ≥3.2 in men. The patients, 117 of whom showed a picture of severe gin- highest bleeding percentage was observed in women gival hyperplasia associated with spontaneous bleeding aged ≥62 and in men aged ≥63. Tables 1 and 2 show and tooth mobility. Of these 117, 62.3% were women frequencies base on the determination of the gingival and the average age was 59,18. bleeding index and tooth mobility.

Table 1: Bleeding index according to Saxer-Mühlemann Index*. Grade Frequency Percentage Cumulative Percentage 1 1 0.9 0.9 2 19 16.2 17.1 3 66 56.4 73.5 4 31 26.5 100.0 Total 117 100.0 100.0 *All patients with severe gingival hyperplasia were evaluated for gingival tooth bleeding (n=117).

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Table 2: Tooth Mobility according to Nyman-Lindhe index*. Grade Frequency Percentage Cumulative Percentage 1 8 6.8 6.8 2 55 47.0 53.8 3 54 46.2 100.0 Total 117 100.0 100.0 *All patients with severe gingival hyperplasia were evaluated for tooth mobility.

Analyzing the data looking for the prevalence among However, we believe that the significance of our fin- these patients, the correlation test revealed a highly dings (Pearson correlation coefficient 0.361, p<0.001) significant correlation between gingival bleeding- in could be diminished by the fact that periodontitis is the dex and age, with a Pearson correlation coefficient of most common chronic inflammatory condition suffered 0.361 (p<0.001). No significant association was found by people over the age of 65 (60%) and that it usually between age and tooth mobility (Pearson correlation co- appears in the form of gum bleeding (9). efficient 0.001,p =0.995). Hence, this study highlights that, while there is no sig- In this study, 1.7 % (n=2) of the patients subjected to nificant correlation between gingival bleeding index the specific protocol established (SEPA Code 4), spe- and suffering from AML, there could be a certain trend cifically, a woman and a man with a mean age of 66, between increased bleeding and AML. We believe that were diagnosed with AML. Both patients scored 3 on the even without a significant correlation from a statistical bleeding index and were assessed with degree 4 tooth point of view but with a trend (0.054), there is a clinical mobility, which are the highest Saxer-Mühlemann and one that need to be reported, as far as we know, for the Nyman-Lindhe indexes, respectively. first time. Nevertheless, we are aware that, to substantia- A correlation test was run to demonstrate the association te this association, it would be necessary to increase the between the presence or absence of AML and gingival number of cases studied, which would probably require bleeding and tooth mobility degrees. The Pearson co- the design of a prospective study. rrelation coefficient yielded by the analysis was 0.179, with an associated probability of 0.054, which, we be- Conclusions lieve, shows a trend towards association between high Protocolized assessment of gingival hyperplasia by gingival bleeding index scores and suffering from AML. dentists and clinicians, alongside a close collaboration The same test was used to check whether there was any between them and an increase in the number of multi- association between suffering from AML and dental centric collaborative studies could lead, under certain mobility, obtaining a statistical figure of 0.131 with an circumstances, to an early diagnosis of AML. associated p-value of 0.160. References Discussion 1. Albandar JM, Susin C, Hughes FJ. Manifestations of systemic To our knowledge, the scientific literature produced diseases and conditions that affect the periodontal attachment appa- ratus: Case definitions and diagnostic considerations. J Periodontol. to date includes no extensive studies linking gingival 2018;89:S183-S203. hyperplasia to AML, since most of those available refer 2. Chapple ILC, Mealey BL, Van Dyke TE, Bartold PM, Dommisch only to the description of isolated clinical cases. Only H, Eickholz P, et al. Periodontal health and gingival diseases and con- Busjan et al (5), in a cross-sectional study, compared ditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of the oral mucosa lesions of 39 patients suffering from Periodontal and Peri-Implant Diseases and Conditions. J Periodontol. leukemia with those of 38 healthy patients, observing 2018;89:S74-S84. that 68% of the leukemia patients presented oral mucosa 3. Socransky SS, Haffajee AD, Smith C, Dibart S. Relation of counts lesions, gingival hyperplasia being this study the most of microbial species to clinical status at the sampled site. J Clin Perio- dontol. 1991;18:766-75. important finding. 4. Löwenberg B, Downing JR, Burnett A. Acute myeloid leukemia. N Gürkan et al., (8) classify gingival tissue enlargement as Engl J Med. 1999;341:1051-62. hereditary, secondary to prolonged drug therapy (anticon- 5. Busjan R, Hasenkamp J, Schmalz G, Haak R, Trümper L, Ziebolz vulsants, antihypertensive drugs, calcium channel-bloc- D. Oral health status in adult patients with newly diagnosed acute leukemia. Clin Oral Investigations. 2018;22:411-18. king drugs and immunosuppressive drugs) and resulting 6. Mühlemann HR, Saxer UP. Assumptions in dental hygiene motiva- from different pathological reactions, including under the tion. Quintessenz J. 1981;11:13-8. latter a series of causes that contribute to gingival over- 7. Nyman S, Lindhe J. Examination of Patients with Periodontal Di- growth, leukemic cell infiltration among them. sease. In: Lindhe J, Karring T, Lang N (eds.) Clinical Periodontology

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Funding There is not funding to mention

Ethical approval This study was approved by the Bioethics Committee of the University of Salamanca in accordance with the Helsinki Declaration of 1964. Informed and written consent, formalized at the dental clinic, was obtained from all the patients participating in the study.

Conflict of interest The authors declare that they have no conflict of interest.

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